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目的研究多剂量口服硝苯地平缓释片在人体内的药动学特点和两种硝苯地平缓释片的生物等效性。方法22名健康男性志愿者采用双周期交叉、自身对照试验设计。以尼群地平为内标,采用高效液相色谱-大气压化学源-质谱联用(HPLC-MS)的方法,测定人血浆中硝苯地平的浓度。将22名受试者的经时血药浓度录入DAS(ver 1 .0)程序,得到药代动力学参数,并进行统计分析和生物等效性评价。结果多剂量口服20 mg×7 d受试和参比制剂后血浆中硝苯地平的Cmax分别为52 .5±27 .4、54 .0±31 .2 ng·ml-1,Cmin分别为5 .4 ± 4 .1、6 .2 ±5 .9 ng·ml-1,Cav分别为16 .8 ± 9 .2、19 .3 ±12 .4 ng·ml-1,Tmax分别为3 .7±0 .9、4 .1±1 .1 h,t1/2分别为8 .9±4 .9、8 .5±3 .1 h,AUC0 -τ分别为403 .4±221 .0、461 .9±296 .6 ng·h·ml-1,AUC0 -36h分别为444 .4±256 .1、503 .1±330 .9 ng·h·ml-1,AUC0 -∞分别为482 .1±268 .9、542 .3±348 .4 ng·h·ml-1,DF分别为(299 .8±117 .7) %、(279 .2±97 .5) %。Tmax进行非参数秩和检验,Cmax、Cmin、Cav、DF、AUC0 -τ、AUC0 -36h、AUC0 -∞经对数转换后做方差分析,并经双向单侧t检验,两制剂的Tmax、Cmax、Cmin、Cav、DF、AUC0 -τ、AUC0 -36h、AUC0 -∞均无显著性差异(P>0 .05) ,受试制剂的Cav、DF、AUC0 -36h、AUC0 -τ、AUC0 -∞的90 %可信限落在参比制剂的80 % ~125 %范围内;Cmax、Cmin的90 %可信限落在参比制剂的70 %~143 %范围内。两种制剂的相对生物利用度为(100 .6 ±38 .6) %(AUC0 -36h,T/AUC0 -36h,R×100 %)。结论两种制剂具有生物等效性。
Objective To study the pharmacokinetic characteristics of multi-dose oral nifedipine sustained-release tablets in humans and the bioequivalence of two nifedipine sustained-release tablets. Methods Twenty-two healthy male volunteers were enrolled in a double-cycle crossover, self-controlled trial design. Using nitrendipine as internal standard, the concentration of nifedipine in human plasma was determined by HPLC-MS-MS. Twenty-two subjects were enrolled in the DAS (ver 1.0) program over time to derive pharmacokinetic parameters for statistical analysis and bioequivalence. Results The Cmax of plasma nifedipine after oral administration of 20 mg x 7 d of test and reference preparations were 52.5 ± 27.4 and 44.0 ± 31.2 ng · ml-1, respectively, with Cmin of 5 .4 ± 4 .1,6. 2 ± 5 .9 ng · ml-1, respectively, Cav of 16.8 ± 9.22,19.3 ± 12.4 ng · ml-1, Tmax were 3.7 ± 0. 9,4. ± 1 .1 h, t1 / 2 were respectively 8 .9 ± 4 .9,8 .5 ± 3 .1 h, AUC0-τ were 403 .4 ± 221 .0,461 .9 ± 296.6 ng · h · ml-1, AUC0 -36h were 444.4 ± 256.1,503.1 ± 330.9 ng · h · ml-1, AUC0 -∞ were 482.1 ± 268. 9,542 .3 ± 348 .4 ng · h · ml-1 and DF were (299.8 ± 117.7)% and (279.2 ± 97.5)%, respectively. Tmax were tested by nonparametric rank sum test. The variance analysis of Cmax, Cmin, Cav, DF, AUC0-τ, AUC0 -36h and AUC0-∞ was performed by logarithmic transformation. Tmax and Cmax (P> 0.05), Cav, DF, AUC0 -36h, AUC0-τ, AUC0-∞, CUC, AUC0- Of the 90% confidence limits fell within the range of 80% to 125% of the reference formulation; 90% confidence limits for Cmax, Cmin fell within the range of 70% to 143% of the reference formulation. The relative bioavailability of the two formulations was (100.6 ± 38.6)% (AUC0 -36h, T / AUC0 -36h, R × 100%). Conclusions Both formulations are bioequivalent.